Our studies of various virologic and immunopathologic processes that occur when viruses and parasites replicate in the ocular microenvironment make up five areas: (1) virus-induced retinal degenerative processes, (2) the possible roles of viruses in human diseases, (3) molecular diagnosis and pathogenesis of cytomegalovirus (CMV) infections in humans, (4) varicella-zoster virus (VZV) infections of the retina, and (5) Toxoplasma gondii infections of the retina. We have established that murine coronavirus can induce ocular disease and may be used as a model system for studying retinal degenerative diseases. This model has many unique features. The virus is capable of inducing an acute infection in the presence of mild retinal vascular inflammation. Initial retinal damage is followed by clearance of infectious virus and progressive retinal degeneration. The retinal degenerative phase of this disease has a persistent virus component, an immune component, and a genetic component. Studies on the immunologic component of retinal degeneration demonstrate that the viral RNA and viral proteins are localized in (cells retinal pigment epithelium (RPE) and ciliary body epithelial cells) that are activated to express major histocompatibility complex (MHC) molecules and adhesion molecules. These data suggest that the autoimmune reactivity may be initiated at this site. This disease may be considered a model for degenerative diseases of the pigment epithelium and photoreceptors in humans. Human cytomegalovirus (CMV) is a herpesvirus that is a major cause of blindness in children born with congenital infections and in immunocompromised individuals. It is difficult to study CMV latency in man. Therefore, cell culture models of CMV replication and latency may provide insight into a rationale for alternative treatment modalities. We identified that CMV replicates in human RPE cells. However, there are a number of distinct differences in virus replication in RPE cells in comparison to human fibroblasts. These may be critical variables in viral persistence and viral activation within the retina.